Department of Medical Cell Biology
Schwann cells regulate angiogenesis and blood vessel structure in native and transplanted pancreatic islets
Sara Ullsten1, Liza Grapensparr1, Monica Sandberg1, Per-Ola Carlsson1.
1Medical Cell Biology, Uppsala University, Uppsala, Sweden
Background: Schwann cells (SCs) are the glial cells of the peripheral nervous system. SCs form a network surrounding the pancreatic islet and may also appear inside the endocrine mass partly associated with capillaries. However, there is limited knowledge about the importance of SCs for islet function and vasculature.
Aim: To investigate the importance of SCs for islet function and vasculature in both native islets and in islets co-transplanted with SCs.
Methods: To study SCs in native islets, mice with SC-specific mitochondrial dysfunction, Tfam (mitochondrial transcription factor A)-SCKO were used. Glucose homeostasis was evaluated by glucose- and insulin tolerance tests and islet function was investigated by glucose stimulated insulin release. In co-transplantation studies, control or SC-bioengineered murine islets were transplanted into the renal subcapsular space of alloxan treated NMRI nu/nu mice. Blood glucose was measured at days 3, 7, 14, 21 and 28 posttransplantation. Glucose tolerance tests were performed at day 30, followed by nephrectomy. Islet morphology was evaluated in both transplants and native islets by immunohistochemistry.
Results: Tfam-SCKO mice had impaired glucose tolerance (4.4% increased AUC, p=0.03) with increased blood glucose levels 30 minutes after glucose administration (15.9±0.7 mmol/l vs 12.6±0.9 in control mice, p=0.05). Increased vascular density and vascular diameter was observed compared to islets from littermate control mice. Also, islets of Tfam-SCKO mice had an ∼70% increased basal insulin release (p=0.03) but no difference in glucose stimulated insulin release. Recipients of co-transplants with islets and SC recovered from hyperglycemia faster (blood glucose 6.5±1.2 mmol/L and 5.7±0.4 mmol/L at day 3 (p=0.05) and 7 (p=0.06) posttransplantation) than control animals (11.0±1.7 mmol/L and 8.1±1.2 mmol/L, respectively). However, at day 30, animals receiving SC-bioengineered islets displayed a glucose disposal rate half of that in recipients of control islet transplants. Serum insulin level was 2-3 times higher in recipients of SC-coated transplants compared with control animals. Immunohistochemistry of these grafts revealed that SC-islets had a lower vascular density (2.4±0.2% compared with 3.7±0.3% in control grafts, p=0.008) and an increased fraction of connective tissue.
Conclusion: SCs located within and surrounding native islets are important for early insulin response to an IV glucose load. SCs are also important for islet vascular structure and in the absence of these cells the vascular diameter increases which in turn affects the secretion of insulin. In transplanted SC-bioengineered islets, the excess of SCs initially retains the islet function, but the cells will also shield from ingrowing vessels. This will limit islet revascularization which negatively affects the long term function of the transplants.
Supported by SRC, NNF, SDF and AFA.
17:30 - 18:30
|Young Investigators Best Mini-Orals Session||Schwann cells regulate angiogenesis and blood vessel structure in native and transplanted pancreatic islets||Plenary Room 1|